Mastocytosis

1. Mastocytosis Proliferation of mast cells accumulation in organs Heterogen. manifestations (spontan. regression x aggresive) Cutaneous Systemic

2. Mastocytosis • 80%: cutaneous - children • several clinicopathological categories • no sex predilection • no codon 816 mutation • good prognosis, spontaneous regression • adults: over 30 years, mostly: assoc. SM 20%: systemic - adults

3. Systemic mastocytosis (SM) • Indolent SM • Aggressive SM • SM + assoc. clonal haematol. disease (AHNMD) Very rare: • Mast cell leukemia • Mast cell sarcoma • Extracutaneous mastocytoma

4. Systemic mastocytosis • Symptoms: • Constitutional • Skin • Mediator • Bone Organ involvement • Bone marrow – almost always (PB rarely) • Spleen, lymph nodes, liver, GIT • Skin : over 50% (if +, indolent course)

5. Systemic mastocytosisdiagnostic criteria (1 + 1 or 3 minor) Major • Multifocal, dense aggregates of mast cells Minor • Atypical mast cells (BM, elsewhere) • KIT point mutation – codon 816 • Co-expression of CD117, CD2 and/or CD25 • Serum total tryptase over 20 ng/ml

6. Systemic mastocytosis – dif. dg. Reactive hyperplasia of mast cells Myeloid and lymphoid tumor (LPL) Interstitial dispersion of mast cells Langerhans cell histiocytosis Dendritic cell sarcoma AML

7. Systemic mastocytosis – genetics treatment • Somatic point mutations of KIT • Tyrosine kinase receptor for stem cell factor (mast cell growth factor) • Asp816Val spont. activation of kit protein (indolent, aggressive SM) – interferon a; cladribine; resistance to imatinib; Phe522Cys;Val560Gly • FIP I like- I- PDGFR a - 4q12 SM with assoc. PB eosinophilia – imatinib mesylate